Maenne Okunola Pharm D Candidate: University of Georgia June 3, 2012 Preceptor Dr. Ali Rahimi

Level of Evidence

Intervention to Decrease Glyburide Use in Elderly Patients With Renal Insufficiency Authors: Aspinall, Zhao, Good, Stone, Boresi, Cox, Bartholomew, Jansen, Guterman, Patino, Rivera-Miranda, Burlingame, Frazer, Sellers, Steele, Witt, Cunningham The American Journal of Geriatric Pharmacotherapy 2011; 9:58-68 This study examines the changes in prescribing of glyburide in elderly patients with decreased renal function and the adverse effects of discontinuing therapy

Background Information Sulfonylureas have an increased rate of hypoglycemia Predisposing factors include renal insufficiency, advanced age, dose, concomitant medications, and beginning new therapy Glyburide is not recommended in patients with CrCl less than 50ml/min Reason for study: Veterans Affairs Center for Medication Safety received a report of severe hypoglycemia associated with glyburide use and the majority of the patients were elderly and renally impaired

Design Uncontrolled observational study 4368 targeted outpatient Veterans and 1886 non- targeted Veterans in the comparison group Targeted Veteran Cohort: SrCr ≥ 2 and age ≥ 65 with prescription of glyburide during April 1- June 30 Non-targeted Veteran Cohort: SrCr ≥ 2 and age ≥ 65 with prescription of glyburide during July 1 to September 3 Duration of study: The date they met requirements of the study to March 31, (longest duration April 1,2007-March 3,2008)

Patient Demographics Targeted group: 77 years, male, Caucasian, 2.5 SrCr, 3.8 Charlson comorbidity index score Non-targeted group: 77 years, male, Caucasian, 2.3 SrCr, 3.5 Charlson comorbidity score

Design Information given to Pharmacy Executives in 21 VA geographic areas on September 4,2007: Compiled collected data from April 1, June 30 of patients age over 65 and SCr of >2 (targeted Veterans) Data on the risk of risk of hypoglycemia of glyburide compared to other sulfonylureas Data on the risk of hypoglycemia of glyburide in patients with renal failure Dosing and monitoring suggestions for patients converted to glipizide Instructions to pharmacy executives to contact providers and inform them of the risk with glyburide and encourage a change in therapy

Data Evaluated Monthly glyburide incidence rate ratios of discontinuation in targeted versus nontargeted groups Variability of glyburide discontinuation rates by geographic area Medication to replace glyburide Patient specific factors associated with stopping glyburide Comparisons of hypoglycemia in patients with and without more severe renal insufficiency

Clinical Endpoints Primary endpoint Changes in glyburide prescribing comparing targeted groups to non-targeted groups A new prescription for a sulfonylurea or no new prescriptions for glyburide 135 days after the prescription date Secondary endpoint: Change in HbA 1c after stopping glyburide Comparison of of hypoglycemia before and after discontinuing glyburide Hospitalization or ER visit

Results - Primary Endpoints - Incidence rate ratios (IRR) for discontinuing glyburide was statistically significantly elevated in the months of September, October, and November for the targeted group compared with the non- targeted group - Remainder of the study the discontinuation rates were not significant IRR95% CI Sep Oct Nov

Results Overall glyburide discontinued in 71.5% of targeted cohort and 56% of the non-targeted cohort Glyburide most commonly switched to glipizide African-American race, SCr, Charlson comorbity score, new glyburide use and the VA regions were all associated with physician discontinuation

Results Secondary endpoints For patients in the targeted group who discontinued glyburide Baseline HbA 1c : 7.17% Baseline - most recent value within 3 months of index date After discontinuation HbA 1c : 7.22% Value 3-9 months after discontinuing glyburide Baseline hypoglycemia rates/1000 person-days: (p-value 0.36) After discontinuation Hpoglycemia: (p-value 0.10)

Results- Renal Comparison SCr ≥ 3mg/dL SrCr 2-3 3mg/dL Pre - intervention hypoglycemia rate 0.169/1000 person days 0.081/1000 person days Post- intervention hypoglycemia rate 0.039/1000 person days 0.075/1000 person days

Conclusion This intervention to target elderly patients with proposed renal insufficiency decreased glyburide use over 3 months without compromising glucose control and without major detrimental effects

Limitations Uncontrolled observational study SrCr was the marker for renal function instead of creatinine clearance Information sent to the targeted group could have had profound effects on the prescribing for the non- targeted group because information could have spread Only looked at the first time glyburide was discontinued although it might have been re-started Hypoglycemia codes may be more strict within the VA versus outside the VA

Importance to Health Care Professionals Continued research to decrease glyburide use in elderly patients with renal insufficiency Risk of hypoglycemia more prevalent in the elderly taking sulfonylurea